Gastritis is gastric mucosal injury accompanied by a significant inflammatory infiltrate. Gastropathy is epithelial or mucosal injury with little or no inflammation, as seen in chemical (reactive) injury from NSAIDs or bile.^[1] Current classification is based on cause, as set out in the Kyoto Global Consensus and the Real-World Gastritis Initiative (RE.GA.IN.).^[2][3]

• Helicobacter pylori infection is the leading cause of chronic gastritis worldwide.
• Autoimmune gastritis is the main non-infectious cause of corpus-restricted atrophic gastritis.
• Reactive (chemical) gastropathy from NSAIDs, aspirin, or bile reflux is the most frequent diagnosis where H. pylori is uncommon.

Less common causes include:

• Lymphocytic, eosinophilic, granulomatous, and collagenous gastritis
• Non–H. pylori infections, mainly in immunocompromised hosts
• Radiation, caustic, and ischemic injury

Life-threatening causes are conditions that can lead to death or permanent disability within 24 hours if left untreated.

• Phlegmonous gastritis and its gas-forming variant, emphysematous gastritis: bacterial infection of the gastric wall with mortality of approximately 40%.^[4]
• Caustic or corrosive ingestion (acids, alkalis)^[1]
• Stress-related mucosal disease in critical illness, major surgery, burns, or trauma. This is an erosive, ischemia- and acid-mediated gastropathy, not true inflammatory gastritis.
• Cytomegalovirus (CMV) and other opportunistic infections in immunocompromised patients, which can present as ulceration with bleeding^[4]

• H. pylori infection^[5]
• Autoimmune gastritis^[6]
• NSAIDs and aspirin, which cause reactive gastropathy^[1]
• Bile (duodenogastric) reflux^[7]

• H. pylori is the most common cause of chronic gastritis worldwide and is a WHO/IARC group 1 carcinogen.^[5]
  • It colonizes approximately 43% of the world population.
  • Infection is usually acquired in childhood and persists for life if untreated.
• It produces chronic active gastritis, which stays asymptomatic for decades in most carriers.^[5]
• Phenotype depends on topography:^[5][8]
  • Antral-predominant gastritis: acid output preserved or high; predisposes to duodenal ulcer.
  • Corpus-predominant gastritis or pangastritis: acid output reduced; predisposes to gastric ulcer, atrophy, and gastric adenocarcinoma.
• Bacterial virulence factors are the main determinants of inflammatory intensity and cancer risk. These are a functional cag pathogenicity island (CagA) and the vacuolating cytotoxin VacA.^[5]
• Long-standing infection drives the Correa cascade:^[9]
  • Non-atrophic gastritis → multifocal atrophic gastritis → intestinal metaplasia → dysplasia → adenocarcinoma.
  • The rate ratio for atrophic gastritis in infected versus uninfected persons is approximately 5.0.
  • Atrophy incidence in uninfected persons is below 1% per year.
• Helicobacter heilmannii is a less common cause of Helicobacter gastritis.^[4]

• Autoimmune gastritis (AIG) is immune-mediated destruction of parietal (oxyntic) cells.^[6][10]
  • It is restricted to the corpus and fundus and spares the antrum, which is the reverse of most H. pylori gastritis.
  • It is not self-limiting.
• Mechanism:^[6]
  • The gastric H⁺/K⁺ ATPase (proton pump) is the major autoantigen.
  • Autoreactive T cells drive parietal cell loss.
  • Anti-parietal cell antibodies (PCA) and anti-intrinsic factor antibodies (IFA) are produced.
• Consequences are hypo- or achlorhydria, loss of intrinsic factor, and hypergastrinemia. These lead to malabsorption of:^[11][12]
  • Iron, causing iron-deficiency anemia (often the earlier presentation, in younger patients)
  • Vitamin B12, causing pernicious anemia (a later presentation, in older patients)
  • Folate and calcium
• AIG accounts for approximately 20–27% of obscure or refractory iron-deficiency anemia.^[12]
• Pernicious anemia is a late complication of AIG, not a synonym for it.^[10]
• Other complications are type 1 gastric neuroendocrine tumors and increased gastric adenocarcinoma risk.^[6][13]
• Epidemiology:^[9]
  • Estimated prevalence is approximately 0.5–2% and rises with age.
  • Women are more often affected.
  • AIG is strongly associated with autoimmune thyroid disease (up to about one-third of these patients have AIG) and type 1 diabetes mellitus.
  • Racial and ethnic variation is less prominent than in H. pylori-associated atrophic gastritis.
• Potential and seronegative AIG are now recognized variants.^[10]
• H. pylori may trigger AIG through molecular mimicry, but this has not been proven.^[6][14]

Histologic features are:^[15][1]

• Foveolar hyperplasia (“corkscrew” glands)
• Lamina propria edema
• Smooth muscle fibers extending into the lamina propria
• Vascular ectasia
• Minimal inflammation

It is the most common histopathologic gastric change in large US biopsy cohorts, and its prevalence rises with age.^[16]

Causes:

• NSAIDs and aspirin are the most common medication cause.^[1][17]
  • Reactive gastropathy is found in up to approximately 45% of regular NSAID users.
  • Injury comes from direct topical damage (independent of prostaglandins) plus cyclooxygenase inhibition, and acid makes it worse.
• Bile (duodenogastric) reflux:^[7][18]
  • In the intact stomach, it injures the antrum.
  • After partial gastrectomy or gastrojejunostomy (Billroth II), it injures the corpus and anastomosis and contributes to gastric stump cancer.
• Other drugs and agents:^[15]
  • Bisphosphonates
  • Oral iron
  • Tetracyclines, especially doxycycline
  • 5-aminosalicylic acid
  • Antiplatelet agents such as clopidogrel
  • Selective serotonin reuptake inhibitors
  • Alcohol^[19]
• Gastrostomy tubes can cause localized reactive injury.^[15]

• Lymphocytic gastritis is associated with celiac disease and H. pylori. Some cases are drug-induced or idiopathic.^[1][20]
• Eosinophilic gastritis is linked to food or allergic sensitization and other allergic mechanisms.^[1]
• Granulomatous gastritis:^[1]
  • Leading identifiable causes are Crohn’s disease and sarcoidosis.
  • Other causes are foreign material and granulomatosis with polyangiitis.
  • Some cases are idiopathic (isolated granulomatous gastritis).
• Collagenous gastritis is rare. Its cause is unknown and may be autoimmune.^[1]

These infections occur mostly in immunocompromised hosts: HIV, transplant, chemotherapy, high-dose corticosteroids, diabetes mellitus, and malnutrition.^[7][4]

• Viral:^[4]
  • CMV is the most common, with characteristic “owl-eye” inclusions.
  • Herpes simplex virus involves the stomach rarely and causes punched-out ulcers.
• Bacterial (non–H. pylori):^[4]
  • Phlegmonous gastritis is caused by Streptococcus, Escherichia coli, Enterobacter, or Proteus.
    • Risk factors are immunosuppression, diabetes, alcoholism, hypochlorhydria, and recent instrumentation.
    • Emphysematous gastritis is the gas-forming variant.
  • Other bacterial causes are mycobacteria, syphilis, and Salmonella.
• Fungal and parasitic:^[1][4]
  • Fungi: Candida, mucormycosis, histoplasmosis, aspergillosis
  • Parasites: anisakiasis, strongyloidiasis
  • These occur mainly with immunocompromise or exposure in endemic areas.

• Radiation therapy to the upper abdomen causes radiation gastropathy.^[1]
• Ingestion of caustic or corrosive agents (acids, alkalis) or other chemical irritants causes direct injury.^[1]
• Gastric hypoperfusion and stress-related mucosal disease are erosive gastropathies, not inflammatory gastritis.

These factors modify disease rather than cause it on their own.

• Tobacco and high-salt diet are cofactors for non-autoimmune atrophic gastritis and accelerate H. pylori-associated atrophy.^[9][21]
• Alcohol contributes to reactive gastropathy.^[19]
• Coffee, acidic beverages, and spicy or fatty foods may provoke dyspeptic symptoms. They are not established causes of histologic gastritis in current classifications.^[3]

^[2][14]